Clinically Relevant Prognostic Markers for Prostate Cancer: The Search Goes On

The management of early-stage prostate cancer continues to present both diagnostic and therapeutic dilemmas to primary care physicians and specialists alike. Prostate cancer alone accounted for about 25% of incident cancer cases in men in the United States in 2008 (1). Based on cases diagnosed from 1996 to 2003, an estimated 91% of these men with newly diagnosed cases are likely to have stage 1 or 2 disease, for which 5-year relative survival chances approach 100%. With such a favorable prognosis, some question the benefit of exposing men with early-stage and low- or moderate-grade prostate cancer to radical therapy (2). Although a Scandinavian randomized trial showed that radical prostatectomy may lead to better overall survival among men with well and moderately differentiated prostate cancer, few of the cases in the trial were detected by screening (3). In the United States, where most cases are screening-detected, the relevance of these trial results to most cases is uncertain.

We now have the recently published 10-year mortality results of the Prostate, Lung, Colon, and Ovarian Cancer Screening Trial and the European Randomized Study of Screening for Prostate Cancer. Within 10 years of trial entry, screening increases the number of cancer cases diagnosed but has no effect on cause-specific mortality. These data suggest that a large fraction of prostate cancer diagnosed by prostate-specific antigen (PSA) screening (stage T1c) represents overdiagnosis, defined as screening detection of cancer that will have no long-term clinical effect (4, 5). However, even when localized prostate cancer is detected early and treated with curative intent, 15% to 20% of patients will have biochemical (PSA) recurrence within 5 years (6). Not all of those who have relapse will die of prostate cancer. The European study shows a small mortality benefit for screening at 10 to 13 …